The ADAM (a disintegrin and metalloproteinase) family consists of transmembrane and secreted proteins that play crucial roles in regulating cell phenotype through their effects on cell adhesion, migration, proteolysis, and signaling. Despite all ADAMs containing metalloproteinase domains, only 13 of the 21 genes in the family encode functional proteases, indicating that protein-protein interactions are critical for the functions of the other eight members. The functional ADAM metalloproteinases are involved in "ectodomain shedding" of various growth factors, cytokines, receptors, and adhesion molecules. ADAM-17, the archetypal activity, is essential for the activation of pro-TNF-α and the generation of active forms of Epidermal Growth Factor Receptor (EGFR) ligands, crucial for epithelial tissue development. Other ADAMs, such as ADAM-10, play significant roles in signaling via the Notch and Eph/ephrin pathways. The ADAM family is fundamental to many developmental and homeostatic processes and is also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, and Alzheimer's disease. This review provides an overview of the current knowledge of human ADAMs, discussing their structure, function, regulation, and disease involvement.The ADAM (a disintegrin and metalloproteinase) family consists of transmembrane and secreted proteins that play crucial roles in regulating cell phenotype through their effects on cell adhesion, migration, proteolysis, and signaling. Despite all ADAMs containing metalloproteinase domains, only 13 of the 21 genes in the family encode functional proteases, indicating that protein-protein interactions are critical for the functions of the other eight members. The functional ADAM metalloproteinases are involved in "ectodomain shedding" of various growth factors, cytokines, receptors, and adhesion molecules. ADAM-17, the archetypal activity, is essential for the activation of pro-TNF-α and the generation of active forms of Epidermal Growth Factor Receptor (EGFR) ligands, crucial for epithelial tissue development. Other ADAMs, such as ADAM-10, play significant roles in signaling via the Notch and Eph/ephrin pathways. The ADAM family is fundamental to many developmental and homeostatic processes and is also linked to pathological states when their functions are dysregulated, including cancer, cardiovascular disease, asthma, and Alzheimer's disease. This review provides an overview of the current knowledge of human ADAMs, discussing their structure, function, regulation, and disease involvement.